title: Catabolism of the human erythrocyte C3b/C4b receptor (CR1, CD35): vesiculation and/or proteolysis?
abstract: Human erythrocytes (E) react by exocytosis of membrane vesicles to various stresses including the fixation of the membrane attack complex of Complement. E from normal individuals loose a notable proportion of their initial number of surface CR1 molecules during the ageing process. An acquired decrease of CR1 on E also occurs in pathological conditions such as Systemic Lupus Erythematosus or AIDS. The present study investigated whether calcium ionophore A23187 (Ca-ion) induced vesicle formation of human E in vitro is responsible for a preferential loss of CR1 as well as whether CR1 molecules at the surface of Ca-ion treated E or vesicles are: (i) functional, (ii) native or protease degraded, or (iii) more clustered than CR1 on native E. A study of E from 137 normal individuals showed that a one-hour Ca-ion induced vesicle formation preferentially removed one third of E surface CR1. Kinetic experiments suggested that all surface CR1 could be removed from E upon longer incubation times. CR1 molecules on vesicles were still able to inhibit Complement activation, and were found in larger clusters than on native E. These data suggest that a significant part of surface CR1 molecules may be removed from E by vesicle formation during the life of E in normal individuals. This phenomenon could be exacerbated in pathological conditions.
authors.affiliation: Laboratoire d'Immunologie, CHU Robert Debré, Reims, France.
authors.forename: X
authors.initials: X
authors.lastname: Dervillez
authors.forename: S
authors.initials: S
authors.lastname: Oudin
authors.forename: M T
authors.initials: MT
authors.lastname: Libyh
authors.forename: T
authors.initials: T
authors.lastname: Tabary
authors.forename: B
authors.initials: B
authors.lastname: Reveil
authors.forename: F
authors.initials: F
authors.lastname: Philbert
authors.forename: F
authors.initials: F
authors.lastname: Bougy
authors.forename: M
authors.initials: M
authors.lastname: Pluot
authors.forename: J H
authors.initials: JH
authors.lastname: Cohen
mesh_terms: D000375:Aging / Q000276:immunology; D000483:Alleles; D000001:Calcimycin / Q000494:pharmacology; D015923:Complement C1r / Q000235:genetics*; D015935:Complement C4b / Q000276:immunology; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D005089:Exocytosis / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D006023:Glycoproteins; D006801:Humans; D007150:Immunohistochemistry; D007476:Ionophores / Q000494:pharmacology; D008854:Microscopy, Electron; D010206:Papain / Q000494:pharmacology; D012150:Polymorphism, Restriction Fragment Length; D011951:Receptors, Complement / Q000187:drug effects*; D017463:Receptors, Complement 3b / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism
chemical_list: D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D007476:Ionophores; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D000001:Calcimycin; D015935:Complement C4b; D015923:Complement C1r; D010206:Papain